The invention is directed to the use and preparation of radioactive arsenic (.sup.72 As) labelled tissue-specific ligands useful in the medical imaging of breast cancer.
Breast cancer is of tremendous societal concern. According to the United States National Cancer Institute, approximately 182,000 new cases of breast cancer will be diagnosed each year; furthermore, the American Cancer Society estimates that 1 out of every 9 women will develop breast cancer at some point during their lives. Therefore, early detection and diagnosis of the disease as well as tracking of existing tumors is of great interest. Diagnostic medical imaging is a tool used for these purposes. In some cases, radioactive isotopes are employed as diagnostic aids. However, a lack of tumor tissue selectivity in the delivery of the radioisotope does not optimize their diagnostic utility.
Therefore, selection of an appropriate delivery ligand is paramount. The delivery of the radioisotope to the desired tissue or site of action is based on the recognition and binding of a small molecule or peptide by a receptor unique to that tissue. If a ligand with a preference for binding to malignant breast tissue is known, conjugation of this ligand to a radioisotope will be of great potential clinical utility. Not only will it be possible to monitor progression of old tumors and discover new ones, but previously undetectable metastases may become visible.
Contemporary medical imaging depends largely upon the use of radioisotopes..sup.2 One of the first clinically employed metals of this type is technetium (Tc). This element was first administered to a human subject in the form of Na.sup.99m TcO.sub.4 in 1961. Despite the rapid progress in development of .sup.99 Tc as a diagnostic aid, organ and cell-specific delivery of the radioactive ligand remains one of the largest challenges in the field. Other radioisotopes including halogens such as .sup.125 I, .sup.131 I and .sup.82 Br and isotopes of various metals including lead, gallium, rhenium, arsenic and copper have also been explored as potential imaging agents. However, simply changing the radioisotope does little to alter site-specific delivery.
A previously successful approach to site-specific receptor probe delivery is through the conjugation of an active agent with an affinity for a specific receptor contained within the tissue of interest to a probe with no inherent biological activity. Attempts have been reported using this methodology for the delivery of radioisotopes to specific areas for medical imaging purposes. One such report is described in WO 92/18536 wherein various radioactive isotopes were attached directly to derivatives and fragments of the peptide pituitary adenylate cyclase-activating polypeptide (PACAP). However, as is stated within that very document, "the great number of different mammalian tissues having PACAP receptors will make selective use of this peptide in medicine very difficult." A slightly more successful agent is an .sup.111 In labeled cyclic octapeptide marketed under the name "OctreoScan" with a purported specificity for abdominal tumors.
Despite publications filed on labeled compounds for medical imaging, much work still remains unfinished. The most difficult part of this process is the selection of an appropriate peptide or small molecule and the subsequent derivitization of this compound in such a manner as to not detrimentally affect its recognition by or binding to its receptor.
It is an object of the present invention to provide a methodology for the preparation of .sup.72 As labelled biologically active molecules and their incorporation into peptides and/or small receptor targeted molecules to provide new imaging and therapeutic agents.
It is a further object of the invention to use the inventive ligands as medical imaging agents.